We have reported that serum and bone marrow from patients with folate deficiency contains folic acid binding protein (FABP). FABP binds oxidized mono and polyglutamates of folate at a specific pH, over a wide range of temperature and appears to be similar to the FABP of human milk, cow's milk and that in the serum and bone marrow of some patients with chronic myeloid leukemia and in some pregnant women. It is apparent that the role of FABP in health and disease must be further elucidated. Our data suggests that FABP is an intracellular folate storage protein and an important regulator of folate uptake into the cell. In the normal cell, FABP is probably saturated with folate and binds a small fraction of free folate as it traverses the cell. In folate deficiency, net folate uptake may increase because of the availability of unsaturated FABP as well as increased dihydrofolate reductase to bind free folate. FABP is probably released during cellular demise and in the normal serum, is mainly saturated with bound folate and thus not readily measureable with exogenous H3 PGA. In folate deficiency, serum FABP is partially unsaturated and thus is measureable with exogenous H3 PGA. Additional data is necessary to support this proposed role of FABP, including the isolation and identification of FABP. Several questions remain to be answered, including; (1) How is the folate bound to FABP released? (2) What cells contain FABP? (3) Where in the cell is FABP located, i.e., the membrane? (4) Is FABP present in the intestinal mucosa or secretions, and is it important for the absorption of food folate? (5) Is FABP important in intracellular folyl polyglutamate metabolism and storage? (6) Can the measurement of FABP be helpful in the diagnosis of folate deficiency? (7) Is FABP disturbed in the malabsorption of folate associated with sprue or patients taking oral contraceptives? Our research will be directed to answer these questions and establish the role of FABP in normal and abnormal folate metabolism.